Expert Review of Clinical Pharmacology最新文献

{"title":"Methotrexate polyglutamates.","authors":"Zhilin Yang, Jiayi Mo, Wenshu Li, Zhigang Zhao, Shenghui Mei","doi":"10.1080/17512433.2024.2416674","DOIUrl":"10.1080/17512433.2024.2416674","url":null,"abstract":"<p><strong>Introduction: </strong>Methotrexate polyglutamates (MTXPGs) are intracellular metabolites of methotrexate (MTX) that play a critical role in the drug's activity, influencing both its efficacy and toxicity. As the exact implications of MTXPGs in these processes remain a subject of debate, a comprehensive review of MTXPGs could provide valuable insights for clinicians and pharmacists, potentially minimizing adverse reactions and enhancing therapeutic outcomes.</p><p><strong>Areas covered: </strong>A comprehensive search of relevant literature was conducted in PubMed and Web of Science databases, including studies from their inception to April 2024. Eligible studies included reviews, clinical trials, and real-world analyses. Additional manual searches and citation reviews were also performed. This review aims to explore MTXPGs with a primary focus on their pharmacokinetics, analytical methods, determinants of drug exposure, and their correlation with MTX efficacy and toxicity.</p><p><strong>Expert opinion: </strong>MTXPGs have not yet garnered significant attention in clinical practice. However, multiple studies have demonstrated a relationship between MTXPGs and the efficacy and toxicity of MTX, suggesting a potential avenue for personalized treatment strategies. Future research should aim to further validate and refine this correlation. Additionally, attention should also be directed toward other metabolites of MTX, which may hold clinical significance.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An overview on disease modifying and symptomatic drug treatments for multiple sclerosis.","authors":"Gloria Dalla Costa, Letizia Leocani, Mariaemma Rodegher, Luca Chiveri, Alessandro Gradassi, Giancarlo Comi","doi":"10.1080/17512433.2024.2410393","DOIUrl":"https://doi.org/10.1080/17512433.2024.2410393","url":null,"abstract":"<p><strong>Introduction: </strong>Multiple sclerosis (MS) is an inflammatory and degenerative autoimmune condition, resulting frequently in a disabling condition. Significant improvements of long-term prognosis have been recently achieved with an early and more aggressive use of disease modifying therapies (DMTs). Addressing the complexity of managing its progressive forms remains a significant challenge.</p><p><strong>Areas covered: </strong>This review provides an update on DMTs for relapsing-remitting MS (RRMS) and progressive MS and their efficacy, safety, and mechanism of action, emphasizing the critical role of biomarkers in optimizing treatment decisions. Moreover, some key information on drugs used to manage symptoms such as pain, fatigue, spasticity and urinary problems will be provided. The literature search was conducted using PubMed, Embase, and Cochrane Library databases covering the period from January 2000 to January 2024.</p><p><strong>Expert opinion: </strong>Major advances have been achieved in the treatment of RRMS. Treatment should start immediately as soon as the neurologist is confident with the diagnosis and its choice should be based on the prognostic profile and on the patient's propensity to accept drug-related risks. The therapeutic landscape for progressive MS is quite disappointing and necessitates further innovation. Personalized medicine, leveraging biomarker insights, holds promise for refining treatment efficacy and patient outcomes.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirzepatide, a novel, dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist for the ongoing diabesity epidemic: the dawn of a new era?","authors":"Imran Rangraze, Dimitrios Patoulias, Paschalis Karakasis, Mohamed El-Tanani, Manfredi Rizzo","doi":"10.1080/17512433.2024.2408753","DOIUrl":"10.1080/17512433.2024.2408753","url":null,"abstract":"","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clozapine for persons with neurodevelopmental disorders: a systematic review and expert recommendations for clinical practice.","authors":"Hélène Verdoux, Clélia Quiles, Jose de Leon","doi":"10.1080/17512433.2024.2410395","DOIUrl":"10.1080/17512433.2024.2410395","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to synthesize the information on the risks and benefits of clozapine prescription for resistant challenging behavior in persons with neurodevelopmental disorders.</p><p><strong>Methods: </strong>Articles were identified with MEDLINE, Web of Sciences, and PsycINFO search from inception through January 2024. The review was restricted to persons with intellectual disability (ID) and/or autism spectrum disorder (ASD) without comorbid psychotic or affective disorder. Data were synthesized narratively.</p><p><strong>Results: </strong>We identified 24 articles (13 case reports, eight chart studies, two controlled studies, one pharmaco-epidemiological study) including 296 patients with ID (<i>n</i> = 222) or ASD (<i>n</i> = 74) (10% aged ≤ 18 years). After clozapine initiation, a decreased frequency of challenging behavior persisting over time was reported in most participants included in clinical studies, and a significant reduction in the number of admissions in the population-based two-year mirror-image study. Adverse drug reactions were those commonly observed with clozapine, i.e. constipation, sedation, and weight gain.</p><p><strong>Conclusions: </strong>Since only four participants were included in the controlled studies, the benefits of clozapine in neurodevelopmental disorders are supported by a body of evidence exclusively drawn from observational studies. Further studies are required to clarify the indications of clozapine with respect to the unmet need induced by resistant challenging behavior.</p><p><strong>Registration: </strong>PROSPERO database registration number CRD42024522343.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of ulinastatin in critical care patients in real world: a retrospective multi-center study.","authors":"Deduo Xu, Yi Shan, Qinghua Liu, Pei Liang, Xin Hao, Jinyuan Zhang, Ze Yu, Wenfang Li, Fei Gao, Xia Tao, Qin Gu, Yabin Ma, Wansheng Chen","doi":"10.1080/17512433.2024.2402433","DOIUrl":"10.1080/17512433.2024.2402433","url":null,"abstract":"<p><strong>Objectives: </strong>Ulinastatin has been applied in various diseases associated with inflammation, but its effectiveness lacks real-world evidence. We aimed to evaluate the effectiveness of ulinastatin based on a real-world database in the intensive care unit (ICU) patients.</p><p><strong>Methods: </strong>This was a retrospective cohort study. ICU patient data from multi-centers in China were collected. Propensity score matching (PSM) was applied. The effectiveness of ulinastatin was evaluated by mortality, length of stay in the ICU and mechanical ventilation duration. Kaplan-Meier method was used to estimate the hazard ratio and plot the survival curve.</p><p><strong>Results: </strong>A total of 2036 patients were analyzed after PSM. Mortality was significantly lower in the ulinastatin group than in the non-ulinastatin group (hazard ratio for death: 0.77; 95% confidence interval: 0.62-0.96; <i>p</i> = 0.018). Ulinastatin significantly reduced mortality at 28 days (10.0% vs. 13.6%), 60 days (13.9% vs. 18.2%) and 90 days (14.7% vs. 18.5%), length of stay in the ICU (median 8.0 d vs. 13.0 d), and mechanical ventilation duration (median 24.0 h vs. 25.0 h; <i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Ulinastatin was beneficial for patients in the ICU, mainly by reducing mortality, length of ICU stay, and mechanical ventilation duration. This study provides evidence of the clinical effectiveness of ulinastatin.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic interaction of quetiapine and lamotrigine - victim and perpetrator?","authors":"Florian Gilleßen, Arnim Johannes Gaebler, Ekkehard Haen, Georgios Schoretsanitis, Justyna Wozniak, Julia C Stingl, Michael Paulzen","doi":"10.1080/17512433.2024.2410400","DOIUrl":"10.1080/17512433.2024.2410400","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to investigate the ambiguous findings of earlier research regarding the reduction of quetiapine plasma levels when combined with lamotrigine, most likely via UDP-glucuronosyltransferase induction by lamotrigine.</p><p><strong>Methods: </strong>One thousand one hundred and fifty samples, divided into four groups of patients receiving either quetiapine immediate- (IR) or extended-release (XR) without or in combination with lamotrigine were compared regarding absolute and dose-adjusted plasma concentrations. Furthermore, samples of intra-individual controls were analyzed.</p><p><strong>Results: </strong>Patients receiving quetiapine IR in combination with lamotrigine showed 31% lower plasma (<i>p</i> = 0.002) and 23% lower dose-adjusted plasma concentrations (<i>p</i> = 0.004) compared to those receiving IR monotherapy. The proportion of patients with quetiapine plasma concentrations below the lower limit of the therapeutic reference range was 50% and 30% in the combination group and in patients receiving monotherapy, respectively (<i>p</i> = 0.03). However, no significant differences regarding plasma concentration (<i>p</i> = 0.13) and dose-adjusted plasma concentration (<i>p</i> = 0.42) were observed in patients with combination vs. monotherapy with the XR formulation of quetiapine. In the intra-individual controls, no trends could be identified, possibly due to insufficient number of samples (<i>p</i> > 0.05).</p><p><strong>Conclusions: </strong>The combination of quetiapine IR with lamotrigine is associated with significantly lower drug concentrations of quetiapine, potentially impacting quetiapine effectiveness. For quetiapine ER, a significant interaction is less likely.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is therapeutic drug monitoring a dancing partner for TNF-α inhibitors in real-world practice? Answers from an updated systematic review and meta-analysis.","authors":"Yang Hu, Zaiwei Song, Yuan Gao, Dan Jiang, Yiwen Ran, Yi Ma, Huibo Li, Rongsheng Zhao","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>This systematic review aimed to determine the effect of therapeutic drug monitoring (TDM) for tumor necrosis factor-α inhibitors (TNF-αI) in immune-mediated inflammatory diseases (IMIDs) based on real-world evidence, as results from published meta-analyses based on randomized controlled trials (RCTs) may not fully capture the nuances of clinical practice due to strict criteria.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and the Cochrane Library up to 1 August 2023. Cohort studies comparing TDM (proactive and reactive) with empirical management were included. Primary outcome was effectiveness [for IBDs: clinical remission; for rheumatic diseases: clinical remission or low disease activity], with certainty of evidence appraised using the GRADE approach. Secondary outcomes included treatment failure, serious adverse events (SAEs), IMIDs-related surgeries or hospitalizations, and anti-drug antibodies (ADAs) development risk.</p><p><strong>Results: </strong>Twenty-four cohort studies were included and almost all were on infliximab. For IBDs, compared with empirical management, proactive TDM significantly improved clinical remission (RR = 1.15, 95% CI = 1.04-1.28), reduced IBDs-related surgeries (RR = 0.46, 95% CI = 0.26-0.81), hospitalizations (RR = 0.60, 95% CI = 0.43-0.83), SAEs (RR = 0.23, 95% CI = 0.07-0.76), and ADAs development risk (RR = 0.34, 95% CI = 0.19-0.60). Reactive TDM significantly lowered hospitalization rates and might be cost-effective. Proactive TDM outperformed reactive TDM in secondary outcomes. For rheumatic diseases, benefits of TDM were inconclusive due to limited evidence.</p><p><strong>Conclusions: </strong>Real-world evidence supports proactive TDM of TNF-αI (particularly infliximab) in IBDs to improve effectiveness, safety, and immunogenicity. However, benefits of TDM for different TNF-αI in other IMIDs remain uncertain.</p><p><strong>Protocol registration: </strong>www.crd.york.ac.uk/ PROSPERO identifier is CRD42022370846.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study.","authors":"Junjun Xu, Jinmeng Li, Meng Chen, Huifang Jiang, Xudong Fan, Yangmin Hu, Haili Shan, Mingdong Yang, Yichao Xu, Yuying Lang, Haibin Dai, Xinjun Cai","doi":"10.1080/17512433.2024.2410385","DOIUrl":"10.1080/17512433.2024.2410385","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting the pharmacokinetics (PK) of nirmatrelvir/ritonavir.</p><p><strong>Methods: </strong>A total of 285 serum samples and clinical data were collected from 152 patients. The PPK models of nirmatrelvir/ritonavir were analyzed using nonlinear mixed-effect modeling (NONMEM) approach. The optimal dosing regimen for patients with different renal function was determined using Monte Carlo simulations.</p><p><strong>Results: </strong>The population typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) of nirmatrelvir were 2.26 L/h and 15.3 L, respectively. Notably, creatinine clearance (CrCL) significantly influenced the PK variation of nirmatrelvir. Monte Carlo simulations suggested that patients with mild-to-moderate renal impairment experienced a 22.0-59.9% increase in the area under the curve (AUC) when they were administered a standard dose of nirmatrelvir compared to those with normal renal function. The AUC in patients with severe renal impairment after administration of 150 mg q12h nirmatrelvir was similar to that in patients with normal renal function after administration of 300 mg q12h nirmatrelvir.</p><p><strong>Conclusions: </strong>PPK modeling and simulation provided a reference for the rational clinical application of nirmatrelvir/ritonavir in critically ill Chinese patients.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amylin analogs for the treatment of obesity without diabetes: present and future.","authors":"Theodoros Panou, Evanthia Gouveri, Djordje S Popovic, Nikolaos Papanas","doi":"10.1080/17512433.2024.2409403","DOIUrl":"https://doi.org/10.1080/17512433.2024.2409403","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity is a pandemic, linked with increased morbidity including diabetes mellitus (DM) and certain cancer types. Amylin is a major regulatory hormone for satiation and food intake perception in humans. Amylin analogs (pramlintide and cagrilintide) are emerging as promising anti-obesity agents in non-DM subjects.</p><p><strong>Areas covered: </strong>Pramlintide, the first amylin analog, initially used for the treatment of both type 1 and type 2 DM, has demonstrated weight-lowering action. Clinical trials confirmed a weight loss exceeding 3% in the study period without major untoward effects, which was maintained beyond the follow-up period. Recently, cagrilintide, a long-lasting synthetic amylin analog has been introduced. Cagrilintide has achieved adequate weight loss, reaching even more than 10% of the total weight in early clinical trials. However, adverse gastrointestinal effects, particularly nausea, were more frequent compared with pramlintide. Clinical trials have also confirmed the effectiveness of cagrilintide in comparison with glucagon-like peptide 1 receptor agonists.</p><p><strong>Expert opinion: </strong>Amylin analogs will certainly enrich the growing therapeutic armamentarium aimed at tackling obesity. The most exciting future research venue could be the development of their combinations with other weight-lowering drugs, especially dual and triple incretin-based co-agonists, thus potentially providing massive weight-loss effects.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing the risk of death - a possible outcome in COPD patients.","authors":"Mauro Maniscalco, Luigino Calzetta, Paola Rogliani, Mario Cazzola","doi":"10.1080/17512433.2024.2408272","DOIUrl":"10.1080/17512433.2024.2408272","url":null,"abstract":"<p><strong>Introduction: </strong>COPD is a leading cause of global mortality, particularly under-recognized and under-diagnosed. In 2020, it was the sixth leading cause of death in the US and has contributed to 4.72% of all-cause mortality (ACM) according to the Global Burden of Disease Study 2017. Factors influencing COPD-related mortality include smoking, aging populations, comorbidities, sarcopenia, physical capacity, and lack of effective treatments.</p><p><strong>Areas covered: </strong>This review discusses various factors influencing COPD-related mortality and analyzes observational studies and pivotal RCTs evaluating the impact of different therapies on ACM.</p><p><strong>Expert opinion: </strong>COPD significantly impacts ACM, necessitating effective management strategies. Smoking cessation is crucial in reducing mortality risk. Exacerbation management and comorbidity treatment are essential to improve patient outcomes. Various therapeutic interventions, such as smoking cessation, vaccination, long-term oxygen therapy, and lung volume reduction surgery, have shown benefits in reducing mortality. Pharmacotherapies might reduce the risk of mortality, although the current scientific evidences remain inconclusive. Advances in pharmacological interventions, tailored treatment plans, and physical activity programs are vital. More robust and long-term studies, focusing on real-world data and addressing biases in treatment allocation, are needed to conclusively determine the efficacy of different therapies in reducing ACM in COPD patients.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}